Differentiation of human embryonic stem cells into hematopoietic cells by coculture with human fetal liver cells recapitulates the globin switch that occurs early in development

Qiu, Caihong; Hanson, Eric T.; Olivier, Emmanuel; Inada, Mari; Kaufman, Dan S.; Gupta, Sanjeev; Bouhassira, Eric E.

doi:10.1016/j.exphem.2005.09.003

Cited by 121 publications

(101 citation statements)

References 43 publications

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“…Multiple reports have subsequently used a variety of stromal cell lines, including OP9, M2-10B4, FH-B-hTERT, and primary human BM stroma, to support hematopoietic development from hESCs. 54,[58][59][60][61] More recent studies have evaluated what soluble or secreted "factors" are important for hematopoietic development in these cultures. Ledran et al 54 demonstrated that coculture of hESCs on AM20.1B4 cell line lead to increased development of severe combined immunodeficient (SCID) mouse-repopulating cells (SRCs), a close surrogate for HSCs.…”

Section: Approaches To Hematopoietic Differentiation From Hescsmentioning

confidence: 99%

“…87 More specific analysis of globin gene expression in erythroid cells derived from hESCs used hESCs cocultured on FH-B or S17 cells. 61 Analysis of mRNA expression from the ␤-globin locus showed that hESC-derived erythroid cells produced ⑀-and ␥-globin mRNAs but only minimal ␤-globin expression. Over time in culture, the mean ratio of ␥/⑀ increased by more than 10-fold, recapitulating the ⑀-globin to ␥-globin switch but not the later ␥-globin to ␤-globin switch.…”

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Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells

Kaufman

2009

Blood

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137

118

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IntroductionA decade has now passed since the first report describing human embryonic stem cells (hESCs) provided an important landmark in studies of stem cell biology. 1 Even that first report shows the potential to use hESCs to study hematopoiesis, because a figure of an hESC-derived teratoma showed bone elements surrounding immature hematopoietic cells. In the past decade, dozens of studies have now described the derivation of essentially all blood cell lineages from hESCs. The foundation for this work rests on decades of previous studies using mouse ESCs (mESCs) and other developmental models. 2,3 These approaches have facilitated our ability to translate basic biologic mechanisms to novel cellular therapies now routinely used for transfusions, hematopoietic cell transplantation, and cell-based immunotherapy.The more recent development of mouse and human induced pluripotent stem cells (iPSCs) also provide other key achievements in the stem cell field. [4][5][6][7][8][9][10] Briefly, iPSCs are produced by reprogramming somatic cells (eg, fibroblasts) by transfer of defined genes using viral or other vectors. 9,10 Initial studies by Yamanaka 4,7 used Oct4, Sox2, Klf4, and c-Myc to derive first mouse and then human iPSCs. Thomson and colleagues 8 found Oct4, Sox2, Nanog, and Lin28 could also produce human iPSCs. iPSCs can now be successfully produced with just 1 or 2 genes, and this gene expression can be done transiently rather than requiring stable genome integration. 9,[11][12][13][14][15][16][17] This premise is further advanced by derivation of iPSCs with the use of protein transduction of appropriate transcription factors. 18,19 In addition, it is possible to convert many different mature cell lineages (including hematopoietic cells) into iPSCs. [20][21][22] In an intriguing related study, transient expression of a limited number of genes can convert one mature cell population into another mature cell population without going through an iPSC intermediary, as shown for conversion of exocrine to endocrine pancreas. 23 iPSCs have essentially the same phenotype, gene expression pattern, and developmental potential as ESCs. Mouse iPSCs can form viable chimeras and contribute to germline cells when injected into mouse blastocytes. 5,24 This demonstration that an entire mouse can be derived from a single mouse iPSC is the most stringent test of pluripotency. Human iPSCs form teratomas with contributions of all 3 germ layers (endoderm, ectoderm, and mesoderm) and have been used to produce many differentiated cell lineages. [6][7][8]25 Human iPSCs may provide an optimal source of patient-specific pluripotent stem cells for derivation of hematopoietic cells (or other cells of interest) suitable for transplantation without concern for immunologic barriers. Recent studies have shown derivation of hematopoietic cells from iPSCs with the same characteristics as those derived from hESCs. 26 Although many questions about iPSCs remain, this technology has proven to be highly reproducible and rapidly evolving to be...

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Section: Approaches To Hematopoietic Differentiation From Hescsmentioning

confidence: 99%

mentioning

confidence: 99%

Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells

Kaufman

2009

Blood

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137

118

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“…Several groups have explored their hematopoietic potential, [5][6][7] although few have focused on erythroblastic differentiation, [8][9][10][11] using complex protocols. One group 11 was able to grow blood types A, B, O, and both Rhesus D positive (RH :1) and Rhesus D negative (RH :-1) but unable to produce the O RH :-1 blood type -the so-called "universal" donor -because none of the hESC lines approved in the USA contain the O-negative gene.…”

Section: Introductionmentioning

confidence: 99%

Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine

Lapillonne¹,

Kobari²,

Mazurier³

et al. 2010

Haematologica

214

253

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The online version of this article has a a Supplementary Appendix. BackgroundEx vivo manufacture of red blood cells from stem cells is a potential means to ensure an adequate and safe supply of blood cell products. Advances in somatic cell reprogramming of human induced pluripotent stem cells have opened the door to generating specific cells for cell therapy. Human induced pluripotent stem cells represent a potentially unlimited source of stem cells for erythroid generation for transfusion medicine. Design and MethodsWe characterized the erythroid differentiation and maturation of human induced pluripotent stem cell lines obtained from human fetal (IMR90) and adult fibroblasts (FD-136) compared to those of a human embryonic stem cell line (H1). Our protocol comprises two steps: (i) differentiation of human induced pluripotent stem cells by formation of embryoid bodies with indispensable conditioning in the presence of cytokines and human plasma to obtain early erythroid commitment, and (ii) differentiation/maturation to the stage of cultured red blood cells in the presence of cytokines. The protocol dispenses with major constraints such as an obligatory passage through a hematopoietic progenitor, co-culture on a cellular stroma and use of proteins of animal origin. ResultsWe report for the first time the complete differentiation of human induced pluripotent stem cells into definitive erythrocytes capable of maturation up to enucleated red blood cells containing fetal hemoglobin in a functional tetrameric form. ConclusionsRed blood cells generated from human induced pluripotent stem cells pave the way for future development of allogeneic transfusion products. This could be done by banking a very limited number of red cell phenotype combinations enabling the safe transfusion of a great number of immunized patients. © F e r r a t a S t o r t i F o u n d a t i o n

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“…The inductive properties of the niche have been used to direct differentiation of ESC to desired lineages. Successful examples include differentiation of hESC to dopaminergic neurons using the stromal cell line PA6 [14] as well as hematopoietic differentiation of both murine and human ESCs to hematopoietic lineages using stromal cells derived from the bone marrow and fetal liver [15][16][17]. In this study, we have endeavored to replicate the LSC niche in vitro using extracellular matrix (ECM) components and limbal fibroblasts and have investigated the effects of the LSC niche into the differentiation capacity of hESCs.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of Human Embryonic Stem Cells into Corneal Epithelial-Like Cells by In Vitro Replication of the Corneal Epithelial Stem Cell Niche

et al. 2007

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Human embryonic stem cells (hESCs) are pluripotent cells capable of differentiating into any cell type of the body. It has long been known that the adult stem cell niche is vital for the maintenance of adult stem cells. The cornea at the front of the eye is covered by a stratified epithelium that is renewed by stem cells located at its periphery in a region known as the limbus. These so-called limbal stem cells are maintained by factors within the limbal microenvironment, including collagen IV in basement membrane and limbal fibroblasts in the stroma. Because this niche is very specific to the stem cells (rather than to the more differentiated cells) of the corneal epithelium, it was hypothesized that replication of these factors in vitro would result in hESC differentiation into corneal epithelial-like cells. Indeed, here we show that culturing of hESC on collagen IV using medium conditioned by the limbal fibroblasts results in the loss of pluripotency and differentiation into epithelial-like cells. Further differentiation results in the formation of terminally differentiated epithelial-like cells not only of the cornea but also of skin. Scanning electron microscopy shows that some differences exist between hESC-derived and adult limbal epithelial-like cells, necessitating further investigation using in vivo animal models of limbal stem cell deficiency. Such a model of hESC differentiation is useful for understanding the early events of epithelial lineage specification and to the eventual potential application of epithelium differentiated from hESC for clinical conditions of epithelial stem cell loss.

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Differentiation of human embryonic stem cells into hematopoietic cells by coculture with human fetal liver cells recapitulates the globin switch that occurs early in development

Cited by 121 publications

References 43 publications

Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells

Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells

Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine

Differentiation of Human Embryonic Stem Cells into Corneal Epithelial-Like Cells by In Vitro Replication of the Corneal Epithelial Stem Cell Niche

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